tbuckley/cabot-search huggingface dataset:
Localized delivery of nanomedicine and antibodies for combating COVID-19
Authors: Bin Tu, Yanrong Gao, Xinran An, Huiyuan Wang, Yongzhuo Huang
Journal: Acta Pharmaceutica Sinica B (2022)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a major health burden in the world. So far, many strategies have been investigated to control the spread of COVID-19, including social distancing, disinfection protocols, vaccines, and antiviral treatments. Despite the significant achievement, due to the constantly emerging new variants, COVID-19 is still a great challenge to the global healthcare system. It is an urgent demand for the development of new therapeutics and technologies for containing the wild spread of SARS-CoV-2. Inhaled administration is useful for the treatment of lung and respiratory diseases, and enables the drugs to reach the site of action directly with benefits of decreased dose, improved safety, and enhanced patient compliance. Nanotechnology has been extensively applied in the prevention and treatment of COVID-19. In this review, the inhaled nanomedicines and antibodies, as well as intranasal nanodrugs, for the prevention and treatment of COVID-19 are summarized.
Mitigating the prevalence and function of myeloid-derived suppressor cells by redirecting myeloid differentiation using a novel immune modulator
Authors: Liliana Oliver, Rydell Alvarez, Raquel Diaz, Anet Valdés, Sean H Colligan, Michael J Nemeth, Danielle Y F Twum, Audry Fernández, Olivia Fernández-Medina, Louise M Carlson, Han Yu, Kevin H Eng, Mary L Hensen, Maura L Rábade-Chediak, Luis Enrique Fernández, Kelvin P Lee, Leslie Perez, Jason B Muhitch, Circe Mesa, Scott I Abrams
Journal: Journal for ImmunoTherapy of Cancer (2022)

Immune suppression is common in neoplasia and a major driver is tumor-induced myeloid dysfunction. Yet, overcoming such myeloid cell defects remains an untapped strategy to reverse suppression and improve host defense. Exposure of bone marrow progenitors to heightened levels of myeloid growth factors in cancer or following certain systemic treatments promote abnormal myelopoiesis characterized by the production of myeloid-derived suppressor cells (MDSCs) and a deficiency in antigen-presenting cell function. We previously showed that a novel immune modulator, termed 'very small size particle' (VSSP), attenuates MDSC function in tumor-bearing mice, which was accompanied by an increase in dendritic cells (DCs) suggesting that VSSP exhibits myeloid differentiating properties. Therefore, here, we addressed two unresolved aspects of the mechanism of action of this unique immunomodulatory agent: (1) does VSSP alter myelopoiesis in the bone marrow to redirect MDSC differentiation toward a monocyte/macrophage or DC fate? and (2) does VSSP mitigate the frequency and suppressive function of human tumor-induced MDSCs? To address the first question, we first used a murine model of granulocyte-colony stimulating factor-driven emergency myelopoiesis following chemotherapy-induced myeloablation, which skews myeloid output toward MDSCs, especially the polymorphonuclear (PMN)-MDSC subset. Following VSSP treatment, progenitors and their myeloid progeny were analyzed by immunophenotyping and MDSC function was evaluated by suppression assays. To strengthen rigor, we validated our findings in tumor-bearing mouse models. To address the second question, we conducted a clinical trial in patients with metastatic renal cell carcinoma, wherein 15 patients were treated with VSSP. Endpoints in this study included safety and impact on PMN-MDSC frequency and function. We demonstrated that VSSP diminished PMN-MDSCs by shunting granulocyte-monocyte progenitor differentiation toward monocytes/macrophages and DCs with heightened expression of the myeloid-dependent transcription factors interferon regulatory factor-8 and PU.1. This skewing was at the expense of expansion of granulocytic progenitors and rendered the remaining MDSCs less suppressive. Importantly, these effects were also demonstrated in a clinical setting wherein VSSP monotherapy significantly reduced circulating PMN-MDSCs, and their suppressive function. Altogether, these data revealed VSSP as a novel regulator of myeloid biology that mitigates MDSCs in cancer patients and reinstates a more normal myeloid phenotype that potentially favors immune activation over immune suppression.
Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor
Authors: S.M. Ashiqul Islam, Marcos Díaz-Gay, Yang Wu, Mark Barnes, Raviteja Vangara, Erik N. Bergstrom, Yudou He, Mike Vella, Jingwei Wang, Jon W. Teague, Peter Clapham, Sarah Moody, Sergey Senkin, Yun Rose Li, Laura Riva, Tongwu Zhang, Andreas J. Gruber, Christopher D. Steele, Burçak Otlu, Azhar Khandekar, Ammal Abbasi, Laura Humphreys, Natalia Syulyukina, Samuel W. Brady, Boian S. Alexandrov, Nischalan Pillay, Jinghui Zhang, David J. Adams, Iñigo Martincorena, David C. Wedge, Maria Teresa Landi, Paul Brennan, Michael R. Stratton, Steven G. Rozen, Ludmil B. Alexandrov
Journal: Cell Genomics (2022)

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for
Risk factors of progression from discoid lupus to severe systemic lupus erythematosus: a registry-based cohort study of 164 patients.
Authors: Lisa Fredeau, Delphine S. Courvoisier, Raphaël Aït Mehdi, Saskia Ingen-Housz-Oro, Emmanuel Mahe, Nathalie Costedoat-Chalumeau, Laurent Arnaud, Camille Francès, Alexis Mathian, Marie Jachiet, Zahir Amoura, Jean David Bouaziz, François Chasset
Journal: Journal of the American Academy of Dermatology (2022)
The diagnostic accuracy of rapid diagnostic tests for Ebola virus disease: a systematic review
Authors: Andrew B. Dagens, Amanda Rojek, Louise Sigfrid, Annette Plüddemann
Journal: Clinical Microbiology and Infection (2022)

BackgroundEbola virus disease (EVD) is a dangerous condition that can cause an epidemic. Several rapid diagnostic tests (RDTs) have been developed to diagnose EVD. These RDTs promise to be quicker and easier to use than the current reference standard diagnostic test, PCR.ObjectivesTo assess the diagnostic accuracy of RDTs for EVD.MethodsA systematic review of diagnostic accuracy studies.Data sourcesThe following bibliographic databases were searched from inception to present: MEDLINE (Ovid), Embase, Global Health, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus database, Web of Science, PROSPERO register of Systematic Reviews, and Clinical Trials.Gov.Study eligibility criteriaDiagnostic accuracy studies.ParticipantsPatients presenting to the Ebola treatment units with symptoms of EVD.InterventionsRDTs; reference standard, RT-PCR.Assessment of risk of biasQuality Assessment of Diagnostic Accuracy Studies-2 tool.Methods of data synthesisSummary estimates of diagnostic accuracy study were produced for each device type. Subgroup analyses were performed for RDT type and specimen material. A sensitivity analysis was performed to assess the effect of trial design and bias.ResultsWe included 15 diagnostic accuracy studies. The summary estimate of sensitivity for lateral flow assays was 86.1% (95% CI, 86–86.2%), with specificity of 97% (95% CI, 96.1–97.9%). The summary estimate for rapid PCR devices was sensitivity of 96.2% (95% CI, 95.3–97.9%), with a specificity of 96.8% (95% CI, 95.3–97.9%). Pre-specified subgroup analyses demonstrated that RDTs were effective on a range of specimen material. Overall, the risk of bias throughout the included studies was low, but it was high in patient selection and uncertain in the flow and timing domains.ConclusionsRDTs possess both high sensitivity and specificity compared with RT-PCR among symptomatic patients presenting to the Ebola treatment units. Our findings support the use of RDTs as a 'rule in' test to expedite treatment and vaccination.
ncFO: A Comprehensive Resource of Curated and Predicted ncRNAs Associated with Ferroptosis
Authors: Shunheng Zhou, Yu’e Huang, Jiani Xing, Xu Zhou, Sina Chen, Jiahao Chen, Lihong Wang, Wei Jiang
Journal: Genomics Proteomics & Bioinformatics (2022)

Ferroptosis is a form of regulated cell death driven by the accumulation of lipid hydroperoxides. Regulation of ferroptosis might be beneficial to cancer treatment. Non-coding RNAs (ncRNAs) are a class of RNA transcripts that generally cannot encode proteins and have been demonstrated to play critical roles in regulating ferroptosis. Herein, we developed ncFO, the ncRNA-ferroptosis association database, to document the manually curated and predicted ncRNAs that are associated with ferroptosis. Collectively, ncFO contains 90 experimentally verified entries, including 46 microRNAs (miRNAs), 21 long non-coding RNAs (lncRNAs), and 17 circular RNAs (circRNAs). In addition, ncFO also incorporates two online prediction tools based on the regulation and co-expression of ncRNA and ferroptosis genes. Using default parameters, we obtained 3260 predicted entries, including 598 miRNAs and 178 lncRNAs, by regulation, as well as 2,592,661 predicted entries, including 967 miRNAs and 9632 lncRNAs, by ncRNA-ferroptosis gene co-expression in more than 8000 samples across 20 cancer types. The detailed information of each entry includes ncRNA name, disease, species, tissue, target, regulation, publication time, and PubMed identifier. ncFO also provides survival analysis and differential expression analysis for ncRNAs. In summary, ncFO offers a user-friendly platform to search and predict ferroptosis-associated ncRNAs, which might facilitate research on ferroptosis and discover potential targets for cancer treatment. ncFO can be accessed at http://www.jianglab.cn/ncFO/.
Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety interim analysis
Authors: Hui Zhang, Chaoke Bu, Zhiyong Peng, Guangchao Li, Zhao Zhou, Wen Ding, Yongwei Zheng, Yingyi He, Zhengbin Hu, Kunlin Pei, Min Luo, Chunfu Li
Journal: Leukemia (2022)
Repeated turnovers keep sex chromosomes young in willows
Authors: Deyan Wang, Yiling Li, Mengmeng Li, Wenlu Yang, Xinzhi Ma, Lei Zhang, Yubo Wang, Yanlin Feng, Yuanyuan Zhang, Ran Zhou, Brian J. Sanderson, Ken Keefover-Ring, Tongming Yin, Lawrence B. Smart, Stephen P. DiFazio, Jianquan Liu, Matthew Olson, Tao Ma
Journal: Genome biology (2022)

Abstract Background Salicaceae species have diverse sex determination systems and frequent sex chromosome turnovers. However, compared with poplars, the diversity of sex determination in willows is poorly understood, and little is known about the evolutionary forces driving their turnover. Here, we characterized the sex determination in two Salix species, S. chaenomeloides and S. arbutifolia , which have an XY system on chromosome 7 and 15, respectively. Results Based on the assemblies of their sex determination regions, we found that the sex determination mechanism of willows may have underlying similarities with poplars, both involving intact and/or partial homologs of a type A cytokinin response regulator ( RR ) gene. Comparative analyses suggested that at least two sex turnover events have occurred in Salix , one preserving the ancestral pattern of male heterogamety, and the other changing heterogametic sex from XY to ZW, which could be partly explained by the “deleterious mutation load” and “sexually antagonistic selection” theoretical models. We hypothesize that these repeated turnovers keep sex chromosomes of willow species in a perpetually young state, leading to limited degeneration. Conclusions Our findings further improve the evolutionary trajectory of sex chromosomes in Salicaceae species, explore the evolutionary forces driving the repeated turnovers of their sex chromosomes, and provide a valuable reference for the study of sex chromosomes in other species.
Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 or mRNA-1273: A population-based cohort study (COVIDENCE UK)
Authors: Giulia Vivaldi, David A. Jolliffe, Hayley Holt, Florence Tydeman, Mohammad Talaei, Gwyneth A. Davies, Ronan A. Lyons, Christopher J. Griffiths, Frank Kee, Aziz Sheikh, Seif O. Shaheen, Adrian R. Martineau
Journal: The Lancet Regional Health - Europe (2022)

Little is known about how demographic, behavioural, and vaccine-related factors affect risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations. This prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence. 1051 (7·1%) of 14 713 post-primary participants and 1009 (9·5%) of 10 665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195–216) and 85 days (66–103), respectively. Primary vaccination with ChAdOx1 (vs BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1·63, 95% CI 1·41–1·88) and after an mRNA-1273 booster (1·26 [1·00–1·57] vs BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0·97 [0·96–0·97] per year; post-booster: 0·97 [0·97–0·98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1·78 [1·44–2·20] for primary/secondary vs postgraduate; post-booster: 1·46 [1·16–1·83]) and at least three weekly visits to indoor public places (post-primary: 1·36 [1·13–1·63] vs none; post-booster: 1·29 [1·07–1·56]). Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations. Barts Charity, UK Research and Innovation Industrial Strategy Challenge Fund.
Genetic dissection of TLR9 reveals complex regulatory and cryptic proinflammatory roles in mouse lupus
Authors: Claire Leibler, Shinu John, Rebecca A. Elsner, Kayla B. Thomas, Shuchi Smita, Stephen Joachim, Russell C. Levack, Derrick J. Callahan, Rachael A. Gordon, Sheldon Bastacky, Ryutaro Fukui, Kensuke Miyake, Sebastien Gingras, Kevin M. Nickerson, Mark J. Shlomchik
Journal: Nature Immunology (2022)
William Lindsay Morrison
Authors: John Morris, Rod Stables
Journal: BMJ (2022)

Background/Aim: The value of androgen receptor (AR) in breast cancer has gained renewed interest as a prognostic and treatment predictive biomarker. The aims of this work were to study the associations and the prognostic value of AR in patients from two clinical cohorts. Materials and Methods: Cohort 1 included 208 premenopausal, node-negative patients of whom 87% had received no adjuvant medical treatment; cohort 2 consisted of 263 patients with stage II disease who had all received 2 years of adjuvant tamoxifen. A semi-quantitative assessment of nuclear AR expression divided into five groups (0-1%, 2-10%, 11-50%, 51-75%, and 76-100%) was performed. Survival analyses, stratified by cohort, were performed using both a trend-test and a cut-off of &gt;10% for positivity. Results: A total of 76% of all patients were AR+, and 89%, 48%, and 23% of the estrogen receptor-positive, negative, and triple-negative, respectively. In Cox regression, stratified by cohort, AR divided into five groups was a prognostic factor for 5-year distant disease-free survival with a hazard ratio of 0.86 per step in fraction score (p=0.018). With a predefined cut-off at 10%, moderate evidence of an effect remained (Hazard Ratio=0.67, p=0.077). In multivariable analysis, AR did not retain an independent prognostic value. Conclusion: AR is a weak, however, not independent prognostic factor for distant metastasis. Although the prognostic value of AR may be questionable, the study identified a subset of AR-positive triple-negative patients as being potential candidates for AR-directed therapy for which further studies are warranted.
Incidence, prevalence and risk factors for low back pain in adolescent athletes: a systematic review and meta-analysis
Authors: Julia Wall, William P Meehan, Katharina Trompeter, Conor Gissane, David Mockler, Nicol van Dyk, Fiona Wilson
Journal: British Journal of Sports Medicine (2022)

Objective To investigate the incidence, prevalence, risk factors and morphological presentations of low back pain (LBP) in adolescent athletes. Design Systematic review with meta-analysis. Data sources Medline, Embase, CINAHL via EBSCO, Web of Science, Scopus. Eligibility criteria for selecting studies Studies evaluating the incidence and/or prevalence of LBP in adolescent athletes across all sports. Results There were 80 studies included. The pooled incidence estimate of LBP in adolescent athletes was 11% (95% CI 8% to 13%, I 2 =0%) for 2 years, 36.0% (95% CI 4% to 68%, I 2 =99.3%) for 12 months and 14% (95% CI 7% to 22%, I 2 =76%) for 6 months incidence estimates. The pooled prevalence estimate of LBP in adolescent athletes was 42% (95% CI 29% to 55%, I 2 =96.6%) for last 12 months, 46% (95% CI 41.0% to 52%, I 2 =56%) for last 3 months and 16% (95% CI 9% to 23%, I 2 =98.3%) for point prevalence. Potential risk factors were sport participation, sport volume/intensity, concurrent lower extremity pain, overweight/high body mass index, older adolescent age, female sex and family history of LBP. The most common morphology reported was spondylolysis. Methodological quality was deemed high in 73% of cross-sectional studies and in 30% of cohort studies. Common reasons for downgrading at quality assessment were use of non-validated survey instruments and imprecision or absence of LBP definition. Summary/conclusion LBP is common among adolescent athletes, although incidence and prevalence vary considerably due to differences in study methodology, definitions of LBP and data collection. PROSPERO registration number CRD42020157206.
Hematopoietic differentiation at single-cell resolution in NPM1-mutated AML
Authors: Matthieu Duchmann, Romane Joudinaud, Augustin Boudry, Justine Pasanisi, Giuseppe Di Feo, Rathana Kim, Maxime Bucci, Clémentine Chauvel, Laureen Chat, Lise Larcher, Kim Pacchiardi, Stéphanie Mathis, Emmanuel Raffoux, Lionel Adès, Céline Berthon, Emmanuelle Clappier, Christophe Roumier, Alexandre Puissant, Claude Preudhomme, Nicolas Duployez, Raphaël Itzykson
Journal: Blood Cancer Journal (2022)
Incidence and survival of neuroendocrine neoplasia in England 1995–2018: A retrospective, population-based study
Authors: Benjamin E. White, Brian Rous, Kandiah Chandrakumaran, Kwok Wong, Catherine Bouvier, Mieke Van Hemelrijck, Gincy George, Beth Russell, Rajaventhan Srirajaskanthan, John K. Ramage
Journal: The Lancet Regional Health - Europe (2022)

Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time.A retrospective, population-based study using nationally representative data between 1995 and 2018 from the National Cancer Registry and Analysis Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized incidence was calculated using Office for National Statistics (ONS) data. Overall survival (OS) was calculated using the Kaplan-Meier estimator. Multivariable analysis was performed using an accelerated failure time model.Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018, highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per 100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In multivariable analysis, age, sex, morphology, stage, site and deprivation were independent predictors of survival (p < 0.001). Survival of the entire cohort, and by primary site, is improving over time.NEN incidence continues to rise in England with survival improving over time. Relatively high survival compared to other cancers is an issue for long-term outcomes and funding of care.Data were extracted and transferred using a grant from Neuroendocrine cancer UK.
Do Thresholds for Invasive Ventilation in Hypoxemic Respiratory Failure Exist? A Cohort Study
Authors: Christopher J. Yarnell, Alistair Johnson, Tariq Dam, Annemijn Jonkman, Kuan Liu, Hannah Wunsch, Laurent Brochard, Leo Anthony Celi, Harm-Jan De Grooth, Paul Elbers, Sangeeta Mehta, Laveena Munshi, Robert A. Fowler, Lillian Sung, George Tomlinson
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Invasive ventilation is a significant event for patients with respiratory failure. Physiologic thresholds standardize the use of invasive ventilation in clinical trials, but it is unknown whether thresholds prompt invasive ventilation in clinical practice. Objectives: To measure, in patients with hypoxemic respiratory failure, the probability of invasive ventilation within 3 hours after meeting physiologic thresholds. Methods: We studied patients admitted to intensive care receiving FiO2 of 0.4 or more via nonrebreather mask, noninvasive positive pressure ventilation, or high-flow nasal cannula, using data from the Medical Information Mart for Intensive Care (MIMIC)–IV database (2008–2019) and the Amsterdam University Medical Centers Database (AmsterdamUMCdb) (2003–2016). We evaluated 17 thresholds, including the ratio of arterial to inspired oxygen, the ratio of saturation to inspired oxygen ratio, composite scores, and criteria from randomized trials. We report the probability of invasive ventilation within 3 hours of meeting each threshold and its association with covariates using odds ratios (ORs) and 95% credible intervals (CrIs). Measurements and Main Results: We studied 4,726 patients (3,365 from MIMIC, 1,361 from AmsterdamUMCdb). Invasive ventilation occurred in 28% (1,320). In MIMIC, the highest probability of invasive ventilation within 3 hours of meeting a threshold was 20%, after meeting prespecified neurologic or respiratory criteria while on vasopressors, and 19%, after a ratio of arterial to inspired oxygen of <80 mm Hg. In AmsterdamUMCdb, the highest probability was 34%, after vasopressor initiation, and 25%, after a ratio of saturation to inspired oxygen of <90. The probability after meeting the threshold from randomized trials was 9% (MIMIC) and 13% (AmsterdamUMCdb). In MIMIC, a race/ethnicity of Black (OR, 0.75; 95% CrI, 0.57–0.96) or Asian (OR, 0.6; 95% CrI, 0.35–0.95) compared with White was associated with decreased probability of invasive ventilation after meeting a threshold. Conclusions: The probability of invasive ventilation within 3 hours of meeting physiologic thresholds was low and associated with patient race/ethnicity.